A realist review of digitally delivered child development assessment and screening tools: Psychometrics and considerations for future use.

BACKGROUND: Developmental screening improves the detection of developmental concerns, yet numerous children are not screened/assessed. Remote child developmental tool administration has been utilized to increase screening and assessment accessibility. METHOD: We conducted a realist review to: (1) identify existing multi-domain child development assessment and screening tools for children 0-5 years; (2) review psychometric data on their digital (i.e., only administered remotely) administration; and (3) explore contextual factors relevant to their digital administration. We searched APA PsycInfo, MEDLINE, CINAHL, and ERIC to identify tools and papers on their psychometrics. We reference-searched included articles and searched Google for relevant grey literature. RESULTS: Of 33 multi-domain child development tools identified in objective one, five tools (in five studies) were delivered digitally and compared to traditional (e.g., paper) delivery (i.e., objective two). Studies evaluated within-group equivalence reliability (k = 2) and between-group equivalence (k = 3). Within-group equivalence reliability was established for the Vineland Adaptive Behavior Scales, and domains (e.g., gross motor) of the Ages and Stages Questionnaires 2nd edition (ASQ-2) and Revised Prescreening Denver Questionnaire (R-PDQ). Between group equivalence was demonstrated for Developmental Neuropsychological Assessment, 2nd Edition (NEPSY-II) subtests and Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-3) items. In another between group evaluation, web-based and paper versions of the ASQ-2 were deemed generally equivalent. Digital Bayley-3 inter-observer reliability ranged from 0.82 to 1.0. Examiner support, time, tool modifications, family resources, and comfort promotion supported digital administration. CONCLUSION: Digitally delivered ASQ-2, R-PDQ, Vineland, and Bayley-3 and NEPSY-II components show promise for equivalence with traditional administration.

Impacts of Parental Technoference on Parent-Child Relationships and Child Health and Developmental Outcomes: A Scoping Review.

Parental technological immersion during parenting activities has been shown to alter parent-child interactions. This concept, referred to as parental technoference, has the potential to affect parent-child relationships and children's health and development. This scoping review utilized the Joanna Briggs Institute (JBI) methodology to identify, describe, and summarize: (a) evidence of parental technoference on parent-child relationships, and children's health and development; (b) definitions and measurements of parental technoference; (c) research designs and methodologies used to investigate parental technoference; and (d) literature gaps. We searched MEDLINE, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database for Systematic Reviews, JBI EBP Database, Embase, CINAHL, and Scopus, as well as the reference lists of included studies for literature on parental technology use during parenting and parent-child interactions and its effects on parent-child relationships, and children's health and development. Sixty-four studies, found in 61 publications, met the review criteria. The effect of parental technoference on parent-child relationships was most studied, and findings demonstrated that parents recognized, and researchers observed, changes in parents' and children's behaviors. Adolescent self-reported mental health concerns and maladaptive technological behaviors (e.g., cyberbullying) were associated with more parental technoference, and findings highlighted safety concerns for children. Other aspects of children's development, although less studied, were also negatively impacted by parental technoference. No significant associations were found between parental technoference and children's medical and physiological health, yet these associations were the least studied. Additional research is needed to understand these associations and evaluate interventions designed to mitigate technoference harms.

Recruitment and Retention Strategies for Parents Experiencing Vulnerability: Lessons from an Online Parenting Program.

BACKGROUND: Supportive parenting programs can promote parent-child interactions and children's development. However, families experiencing vulnerability (e.g., low socioeconomic status) report barriers (e.g., transportation, distrust of researchers) to research participation, and attrition rates of 40% and higher have been reported in parenting research. In response, we conducted a longitudinal evaluation of a digital parenting program in a major metropolitan centre in western Canada and retained 99% of our sample. AIM: Review recruitment and retention strategies employed in the First Pathways study and evaluate associations between sociodemographic (e.g., income) and psychosocial (e.g., parental depression) factors with recruitment and retention strategies. METHODS AND FINDINGS: In collaboration with community agencies, we commenced recruitment of 100 families experiencing vulnerability (e.g., low-income) in June 2021. We utilized strategies to engage staff (e.g., presentations, gift cards, updates) and employed snowball sampling. Families recruited through community agencies were significantly more likely to experience vulnerability (e.g., low income and education, high adverse experiences) compared to families in the snowball sample. We incorporated strategies to minimize participant burden (e.g., choice of online or in-person meetings), promoted rapport (e.g., holiday texts, nonjudgmental environment), incorporated trauma-informed practices (e.g., sensitive inquiry), and demonstrated appreciation for participants' contributions (i.e., honorarium). Family experiences of vulnerability (i.e., low income, depressive symptoms, adversity) were correlated with higher participant rescheduling. CONCLUSION: Nurses need knowledge of strategies to promote equitable access to research for families experiencing vulnerability. Digital programs with protocols designed to establish rapport, include trauma-informed practices, and minimize participant burden will likely optimize participation and retention.

History of "Serve and Return" and a Synthesis of the Literature on Its Impacts on Children's Health and Development.

Parent/caregiver sensitivity and responsiveness are important for children's health and development. The "serve and return" metaphor was created to help providers and caregivers understand the importance of sensitive and responsive early caregiving. In this review, we explain the concept of "serve and return", outline historical and theoretical principles that culminated in this metaphor, highlight parent and child constructs associated with "serve and return" interactions, and synthesize literature on sensitive and responsive caregiving and children's health and developmental outcomes. Nurses and other healthcare professionals in public policy, clinical, community, education, and research roles need knowledge of "serve and return" interactions.

Immature neurons in the primate amygdala: Changes with early development and disrupted early environment.

In human and nonhuman primates, the amygdala paralaminar nucleus (PL) contains immature neurons. To explore the PL's potential for cellular growth during development, we compared PL neurons in (1) infant and adolescent macaques (control, maternally-reared), and in (2) infant macaques that experienced separation from their mother in the first month of life compared to control maternally-reared infants. In maternally-reared animals, the adolescent PL had fewer immature neurons, more mature neurons, and larger immature soma volumes compared to infant PL. There were also fewer total neurons (immature plus mature) in adolescent versus infant PL, suggesting that some neurons move out of the PL by adolescence. Maternal separation did not change mean immature or mature neuron counts in infant PL. However, across all infant animals, immature neuron soma volume was strongly correlated with mature neuron counts. TBR1 mRNA, a transcript required for glutamatergic neuron maturation, is significantly reduced in the maternally-separated infant PL (DeCampo et al., 2017), and was also positively correlated with mature neuron counts in infant PL. We conclude that immature neurons gradually mature by adolescence, and that the stress of maternal separation may shift this trajectory, as revealed by correlations between TBR1 mRNA and mature neuron numbers across animals.

Immature neurons in the primate amygdala: changes with early development and disrupted early environment.

In human and nonhuman primates, the amygdala paralaminar nucleus (PL) contains immature neurons. To explore the PL’s potential for cellular growth during development, we compared PL cells in 1) infant and adolescent macaques (control, maternally-reared), and in 2) infant macaques that experienced separation from their mother in the first month of life. In maternally-reared animals, the adolescent PL had fewer immature neurons, more mature neurons, and larger immature soma volumes compared to infant PL. There were also fewer total neurons (immature plus mature) in adolescent versus infant PL, suggesting that some neurons move out of the PL by adolescence. Maternal separation did not change mean immature or mature neuron counts in infant PL. However, across all infant animals, immature neuron soma volume was strongly correlated with mature neuron counts. tbr-1 mRNA, a transcript required for glutamatergic neuron maturation, is significantly reduced in the maternally-separated infant PL (DeCampo et al, 2017), and was also positively correlated with mature neuron counts in infant PL. We conclude that immature neurons gradually mature by adolescence, and that the stress of maternal separation may shift this trajectory, as revealed by correlations between tbr1mRNA and mature neuron numbers across animals.

Mechanisms by Which Cultural-Centric Narrative Influences Interest in ADRD Research Among African American Adults.

BACKGROUND AND OBJECTIVES: Insufficient ethnoracial diversity is a pervasive challenge in Alzheimer's disease (AD) research. The Recruitment Innovations for Diversity Enhancement (RIDE) is grounded in the premise that culturally informed narratives of research participation can inspire individuals from a given culture-sharing group to consider research enrollment. This study examines factors associated with interest in AD research among Black or African American adults following exposure to RIDE narrative campaign materials. RESEARCH DESIGN AND METHODS: A community-based sample of 500 Black or African American adults viewed RIDE narrative materials online and completed a survey of perceptions about research, AD risk, and likelihood of enrolling in AD research. Logistic regression examined predictors and mediators of self-reported likelihood of participating in AD research. RESULTS: Most (72%) participants reported interest in being contacted for AD research opportunities. After controlling for key variables, prior experience with clinical research and trust in medical researchers emerged as independent predictors of likelihood of enrolling in AD research. Perceived burden of AD research partially mediated the effects of prior research experience and trust on likelihood of enrollment. Perceived benefits of AD research also played a mediating role, accounting for over one third of the effect of trust on likelihood of enrollment. DISCUSSION AND IMPLICATIONS: This study advances the field's understanding of how narrative may function to enhance diversity in AD research. Findings suggest that participant narratives should address experiences regarding the burdens and potential benefits of AD research participation as these factors may influence decisions leading to subsequent research enrollment.

Association between maternal reflective function and preschool children's cognitive abilities.

Children's cognitive abilities (e.g., working memory) are associated with mental health, adaptive behaviors, and academic achievement, and may be enhanced by parental reflective function (i.e., capacity to reflect on mental states, feelings, thoughts, and intentions in one's child and oneself). We evaluated associations between maternal reflective function and children's cognitive abilities alone and while controlling for parent-child attachment and interaction quality, and psychosocial (i.e., maternal depressive symptoms, adverse childhood experiences) and sociodemographic (e.g., socioeconomic status) factors. Our sample, recruited in Canada, was primarily white and included 73 mothers and their 4-5 year old preschool children. Maternal reflective function was measured with the Reflective Functioning Scale applied to the Parent Development Interview and the Parental Reflective Functioning Questionnaire. Multiple regression analyses revealed that maternal reflective function was associated with children's cognitive abilities. The Parent Development Interview rated child-reflective function was associated with children's higher verbal comprehension alone and while adjusting for covariates (e.g., parent-child interaction quality, socioeconomic status), and the Parental Reflective Functioning Questionnaire Interest and Curiosity with higher verbal comprehension while adjusting for parent-child interactions and attachment pattern. The Parental Reflective Functioning Questionnaire Certainty in Mental States was associated with higher working memory scores for children while adjusting for covariates. Full Scale IQ and Visual Spatial Index were not significantly associated with maternal reflective function. Associations were found between secure and disorganized attachment with higher verbal comprehension and lower working memory, respectively. These findings highlight the importance of high maternal reflective function to cognitive abilities in early childhood.

Research Summit V: Optimizing Transitions From Infancy to Early Adulthood in Children With Neuromotor Conditions.

PURPOSE: The purpose of this executive summary is to review the process and outcomes of the Academy of Pediatric Physical Therapy Research Summit V, "Optimizing transitions from infancy to young adulthood in children with neuromotor disabilities: biological and environmental factors to support functional independence." SUMMARY OF KEY POINTS: An interdisciplinary group of researchers, representatives from funding agencies, and individuals with neuromotor disabilities and their parents participated in an intensive 2.5-day summit to determine research priorities to optimize life transitions for children with neuromotor disabilities. Recommended priorities for research included (1) promoting self-determination and self-efficacy of individuals with neuromotor disabilities and their families, (2) best care at the right time: evidence-based best practice care, led and navigated by families seamlessly across the lifespan, (3) strengthening connections between developmental domains to enhance function and participation, and (4) optimal dosing and timing to support adaptive bone, muscle, and brain plasticity across the lifespan.

Neuro-pharmacological reinstatement of ovulation and associated neurobiology in a macaque model of functional hypothalamic amenorrhoea.

STUDY QUESTION: What is the underlying neuropathology in a cynomolgus macaque model of functional hypothalamic amenorrhoea (FHA) and can it be normalized to restore ovulation? SUMMARY ANSWER: Anovulatory monkeys exhibited increased hypothalamic norepinephrine (NE), kisspeptin and gonadotropin-releasing hormone (GnRH) in the early follicular phase, but administration of the NE reuptake inhibitor (NRI), reboxetine (REB), restored ovulation during stress and normalized NE, kisspeptin and GnRH. WHAT IS KNOWN ALREADY: Female cynomolgus macaques, like women, show individual reproductive sensitivity to modest psychosocial and metabolic stress. During stress, resilient females ovulate through two menstrual cycles whereas stress-sensitive (SS) macaques immediately cease ovulation. On Day 5 of a non-stressed menstrual cycle, resilient macaques have less NE synthesizing enzyme [dopamine ß-hydroxylase (DBH)], kisspeptin and GnRH innervation of the medial basal hypothalamus but more endogenous serotonin than SS macaques. Stress increased DBH/NE, kisspeptin and GnRH but did not alter serotonin. STUDY DESIGN, SIZE, DURATION: In a longitudinal design, 27 adult (7-13 years) female cynomolgus macaques (Macaca fascicularis) with three different levels of sensitivity to stress were monitored with daily vaginal swabs and frequent serum progesterone (P) measurements. Three 90-day experimental periods called 'Cycle Sets' were monitored. A Cycle Set consisted of one ovulatory menstrual cycle without stress, and two cycles, or 60 days, with modest stress. Each Cycle Set was followed by a rest period. During a Cycle Set, individuals were either untreated (placebo) or administered escitalopram (CIT) or REB. Ultimately, half of each sensitivity group was euthanized during stress with CIT or REB treatment and the hypothalamus was obtained. Neurobiological endpoints were compared between CIT and REB treatment groups in stress resilient and SS monkeys. PARTICIPANTS/MATERIALS, SETTING, METHODS: The monkeys were housed at the University of Pittsburgh primate facility for the duration of the experiments. Upon euthanasia, their brains and serum samples were shipped to the Oregon National Primate Research Center. The hypothalamus was examined with immunohistochemistry for the expression of DBH (a marker for NE axons), kisspeptin and GnRH. P was measured in the serum samples by radioimmunoassay. MAIN RESULTS AND THE ROLE OF CHANCE: Daily administration of REB restored ovulation in 9 of 10 SS animals during stress. Of note, REB significantly increased P secretion during stress in the most sensitive group (P = 0.032), which indicates ovulation. CIT lacked efficacy. REB significantly reduced DBH/NE, kisspeptin and GnRH axon density in the hypothalamus relative to CIT treatment (P = 0.003. 0.018 and 0.0001, respectively) on Day 5 of the menstrual cycle in resilient and sensitive groups. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The US FDA has not approved REB for human use, although it is used in Europe for the treatment of depression/anxiety as EdronaxTR. Whether REB could be useful for the treatment of FHA in women has not been determined. WIDER IMPLICATIONS FOR THE FINDINGS: The use of an NRI to treat FHA is a novel approach and the potential reinstatement of ovulation could be straightforward compared to current treatment protocols. The underlying neurobiology provides a compelling case for treating the origin of the pathology, i.e. elevated NE, rather than circumventing the hypothalamus altogether with gonadotropins, which have associated risks such as hyperstimulation syndrome or multiple births. STUDY FUNDING/COMPETING INTEREST(S): Portions of this study were supported by NIH grant HD062864 to C.L.B., NIH grant HD62618 to J.L.C. and C.L.B. and 1P51 OD011092 for the operation of the Oregon National Primate Research Center. There were no competing interests.

Evaluating a school-based science program that teaches the physiological effects of nicotine.

School-based drug prevention programs represent a widely endorsed public health goal, with an important aspect of knowledge-based curricula being education about the physiological effects of drugs. Nicotine is one of the world's most addictive substances and in this program we have used nicotine-induced mammalian-like behaviors in flatworms called planarians to successfully teach students (4th-12th grade; n = 1,616 students) about the physiological and addictive effects of nicotine. An initial study tested the change in knowledge about addictive substances in 6th-12th grade students after they completed a lab examining the effects of two concentrations of nicotine on the number of stereotypies (C-shaped spasms) planarians demonstrate in a 5-minute period of time. Lab discussion focused on developing and testing hypotheses, measurement reliability, and mechanisms of nicotine action. Surveys given pre- and post-lab experience showed that 6th grade students have significantly lower knowledge about nicotine than 7th-12th grade students (6th grade: 40.65 ± 0.78% correct, 7th-12th grade: 59.29 ± 1.71%, p < 0.001) pre-lab, but that students in all grades showed a significant increase in knowledge post-lab (p < 0.001). In 6th grade the lab was effective in improving knowledge about nicotine in urban, suburban and rural schools, p < 0.001, with students in suburban schools showing significantly greater knowledge both pre-test (urban: 37.62 ± 1.45%; suburban: 48.78 ± 1.62%; rural: 37.33 ± 0.99%; p < 0.001) and post-test (urban:60.60 ± 1.85%; suburban: 67.54 ± 1.82%; urban: 61.66 ± 1.18%; p < 0.001). A second study, modifying the lab so that the time spent observing the planarians is reduced to a 1-minute period, showed that students in both 4th and 5th grades had a significant increase in knowledge about the physiological and addictive effects of nicotine post-lab (p < 0.001).

Framework for creating storytelling materials to promote African American/Black adult enrollment in research on Alzheimer's disease and related disorders.

INTRODUCTION: African American/Black adults are severely underrepresented in basic, clinical, and behavioral research studies in Alzheimer's disease and related disorders (ADRD). Innovative, evidence-based, and culturally salient strategies can maximize the recruitment of African American/Black adults into ADRD research. METHODS: We conducted and analyzed semi-structured interviews to capture the research participation stories of African American/Black participants and study partners from the University of Pittsburgh's Alzheimer's Disease Research Center. The themes and messaging principles generated through this process informed the development of video- and text-based materials that were evaluated for community member acceptance using focus groups. RESULTS: Focus group individuals (N = 36) generally favorably rated the video and text materials, characterizing them as "interesting," "realistic," and "convincing." DISCUSSION: Capturing the narratives of African American/Black research participants is a critical component to developing culturally relevant materials for broader dissemination and is essential to advancing beyond information-only recruitment approaches, which tend to rely disproportionately on negative messages.

Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults.

OBJECTIVES: Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. METHODS: In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (short and long delay free recall on the California Verbal Learning Test [CVLT]). RESULTS: All the seed regions had significant connectivity within the temporal lobe (including the fusiform, temporal, and lingual gyri). The left CA1 was the only seed with significant functional connectivity to the amygdala. The left entorhinal cortex was the only seed to have significant functional connectivity with frontal cortex (anterior cingulate and superior frontal gyrus). Only higher left dentate-left lingual connectivity was associated with poorer CVLT performance (Spearman r = -0.81, p = 0.0003, Benjamini-Hochberg false discovery rate: 0.01) after multiple comparison correction. CONCLUSIONS: Rather than global hyper-connectivity of the medial temporal lobe, left dentate-lingual connectivity may provide a specific assay of medial temporal lobe hyper-connectivity relevant to memory in aging.

Social Origins of Developmental Risk for Mental and Physical Illness.

Adversity in early childhood exerts an enduring impact on mental and physical health, academic achievement, lifetime productivity, and the probability of interfacing with the criminal justice system. More science is needed to understand how the brain is affected by early life stress (ELS), which produces excessive activation of stress response systems broadly throughout the child's body (toxic stress). Our research examines the importance of sex, timing and type of stress exposure, and critical periods for intervention in various brain systems across species. Neglect (the absence of sensitive and responsive caregiving) or disrupted interaction with offspring induces robust, lasting consequences in mice, monkeys, and humans. Complementary assessment of internalizing disorders and brain imaging in children suggests that early adversity can interfere with white matter development in key brain regions, which may increase risk for emotional difficulties in the long term. Neural circuits that are most plastic during ELS exposure in monkeys sustain the greatest change in gene expression, offering a mechanism whereby stress timing might lead to markedly different long-term behaviors. Rodent models reveal that disrupted maternal-infant interactions yield metabolic and behavioral outcomes often differing by sex. Moreover, ELS may further accelerate or delay critical periods of development, which reflect GABA circuit maturation, BDNF, and circadian Clock genes. Such factors are associated with several mental disorders and may contribute to a premature closure of plastic windows for intervention following ELS. Together, complementary cross-species studies are elucidating principles of adaptation to adversity in early childhood with molecular, cellular, and whole organism resolution.

Long-lasting effect of obesity on skeletal muscle transcriptome.

BACKGROUND: Reduced physical activity and increased intake of calorically-dense diets are the main risk factors for obesity, glucose intolerance, and type 2 diabetes. Chronic overnutrition and hyperglycemia can alter gene expression, contributing to long-term obesity complications. While caloric restriction can reduce obesity and glucose intolerance, it is currently unknown whether it can effectively reprogram transcriptome to a pre-obesity level. The present study addressed this question by the preliminary examination of the transcriptional dynamics in skeletal muscle after exposure to overnutrition and following caloric restriction. RESULTS: Six male rhesus macaques of 12-13 years of age consumed a high-fat western-style diet for 6 months and then were calorically restricted for 4 months without exercise. Skeletal muscle biopsies were subjected to longitudinal gene expression analysis using next-generation whole-genome RNA sequencing. In spite of significant weight loss and normalized insulin sensitivity, the majority of WSD-induced (n = 457) and WSD-suppressed (n = 47) genes remained significantly dysregulated after caloric restriction (FDR ≤0.05). The MetacoreTM pathway analysis reveals that western-style diet induced the sustained activation of the transforming growth factor-ß gene network, associated with extracellular matrix remodeling, and the downregulation of genes involved in muscle structure development and nutritional processes. CONCLUSIONS: Western-style diet, in the absence of exercise, induced skeletal muscle transcriptional programing, which persisted even after insulin resistance and glucose intolerance were completely reversed with caloric restriction.

Maternal deprivation alters expression of neural maturation gene tbr1 in the amygdala paralaminar nucleus in infant female macaques.

Early parental loss is associated with social-emotional dysregulation and amygdala physiologic changes. Previously, we examined whole amygdala gene expression in infant monkeys exposed to early maternal deprivation. Here, we focus on an amygdala region with immature neurons at birth: the paralaminar nucleus (PL). We hypothesized that 1) the normal infant PL is enriched in a subset of neural maturation (NM) genes compared to a nearby amygdala subregion; and 2) maternal deprivation would downregulate expression of NM transcripts (mRNA). mRNAs for bcl2, doublecortin, neuroD1, and tbr1-genes expressed in post-mitotic neurons-were enriched in the normal PL. Maternal deprivation at either 1 week or 1 month of age resulted in PL-specific downregulation of tbr1-a transcription factor necessary for directing neuroblasts to a glutamatergic phenotype. tbr1 expression also correlated with typical social behaviors. We conclude that maternal deprivation influences glutamatergic neuronal development in the PL, possibly influencing circuits mediating social learning.

Western-style diet, with and without chronic androgen treatment, alters the number, structure, and function of small antral follicles in ovaries of young adult monkeys.

OBJECTIVE: To examine the small antral follicle (SAF) cohort in ovaries of adult rhesus monkeys after consumption of a Western-style diet (WSD), with or without chronically elevated androgen levels since before puberty. DESIGN: Cholesterol or T (n = 6 per group) implants were placed SC in female rhesus macaques beginning at 1 year of age (prepubertal), with addition of a WSD (high fat/fructose) at 5.5 years (menarche approximately 2.6 years). Ovaries were collected at 7 years of age. One ovary per female was embedded in paraffin for morphologic and immunohistochemical analyses. The SAFs (<2.5 mm) were dissected from the other ovary obtained at or near menses in a subgroup of females (n = 3 per group) and processed for microarray analyses of the SAF transcriptome. Ovaries of adult monkeys consuming a standard macaque diet (low in fats and sugars) were obtained at similar stages of the menstrual cycle and used as controls for all analyses. SETTING: Primate research center. ANIMAL(S): Adult, female rhesus monkeys (Macaca mulatta). INTERVENTION(S): None. MAIN OUTCOME MEASURES: Histologic analyses, SAF counts and morphology, protein localization and abundance in SAFs, transcriptome in SAFs (messenger RNAs [mRNAs]). RESULT(S): Compared with controls, consumption of a WSD, with and without T treatment, increased the numbers of SAFs per ovary, owing to the presence of more atretic follicles. Numbers of granulosa cells expressing cellular proliferation markers (pRb and pH3) was greater in healthy SAFs, whereas numbers of cells expressing the cell cycle inhibitor (p21) was higher in atretic SAFs. Intense CYP17A1 staining was observed in the theca cells of SAFs from WSD with or without T groups, compared with controls. Microarray analyses of the transcriptome in SAFs isolated from WSD and WSD plus T-treated females and controls consuming a standard diet identified 1,944 genes whose mRNA levels changed twofold or more among the three groups. Further analyses identified several gene pathways altered by WSD and/or WSD plus T associated with steroid, carbohydrate, and lipid metabolism, plus ovarian processes. Alterations in levels of several SAF mRNAs are similar to those observed in follicular cells from women with polycystic ovary syndrome. CONCLUSION(S): These data indicate that consumption of a WSD high in fats and sugars in the presence and absence of chronically elevated T alters the structure and function of SAFs within primate ovaries.

Cytogenesis in the adult monkey motor cortex: perivascular NG2 cells are the major adult born cell type.

We used confocal microscopy and immunohistochemistry (IHC) to look for new cells in the motor cortex of adult macaque monkeys that might form the cellular bases of improved brain function from exercise. Twenty-four female Macaca fascicularis monkeys divided into groups by age (10-12 years, 15-17 years), postexercise survival periods, and controls, received 10 weekly injections of the thymidine analog, bromodeoxyuridine (BrdU) to mark new cells. Sixteen monkeys survived 15 weeks (5 weeks postexercise) and 8 monkeys survived 27 weeks (12 weeks postexercise) after initial BrdU injections. Additionally, five Macaca mulatta female monkeys (∼5.5-7 years) received single injections of BrdU and survived 2 days, 2 weeks, and 6 weeks after BrdU injections. Neural and glial antibodies were used to identify new cell phenotypes and to look for changes in proportions of these cells with respect to time and experimental conditions. No BrdU(+) /DCx(+) cells were found but about 7.5% of new cells were calretinin-positive (Cr(+) ). BrdU(+) /GABA(+) (gamma-aminobutyric acid) cells were also found but no new Cr(+) or GABA(+) cells colabeled with a mature neuron marker, NeuN or chondroitin sulfate antibody, NG2. The proportion of new cells that were NG2(+) was about 85% for short and long survival monkeys of which two, newly described perivascular phenotypes (Pldv and Elu) and a small percentage of pericytes (2.5%) comprised 44% and 51% of the new NG2(+) cells, respectively. Proportions of NG2(+) phenotypes were affected by post-BrdU survival periods, monkey age, and possibly a postexercise sedentary period but no direct effect of exercise was found.

Exposure of female macaques to Western-style diet with or without chronic T in vivo alters secondary follicle function during encapsulated 3-dimensional culture.

Increased adiposity and hyperandrogenemia alter reproductive parameters in both animal models and women, but their effects on preantral follicles in the ovary remain unknown. We recently reported that Western-style diet (WSD) consumption over 1 year, with or without chronic exposure to elevated circulating T, increased the body fat percentage, elicited insulin resistance, suppressed estradiol and progesterone production, as well as altered the numbers, size, and dynamics of antral follicles in the ovary during the menstrual cycle in female macaques. Therefore, experiments were designed to compare the WSD and WSD+T effects to age-matched controls on the survival, growth, and function of isolated secondary follicles during 5 weeks of encapsulated 3-dimensional culture. Follicle survival significantly declined in the WSD and WSD+T groups compared with the control (CTRL) group. Although media progesterone levels were comparable among groups, androstenedione and estradiol levels were markedly reduced in the WSD and WSD+T groups compared with the CTRL group at week 5. Anti-Müllerian hormone levels peaked at week 3 and were lower in the WSD+T group compared with the WSD or CTRL group. Vascular endothelial growth factor levels also decreased at week 5 in the WSD+T group compared with the WSD or CTRL group. After human chorionic gonadotropin exposure, only antral follicles developed from the CTRL group yielded metaphase II oocytes. Thus, WSD with or without T exposure affects the cohort of secondary follicles in vivo, suppressing their subsequent survival, production of steroid hormones and local factors, as well as oocyte maturation in vitro.